DPPA2沉默对胃癌细胞生物学行为的影响  

Effect of DPPA2 gene silencing on the biological behavior of gastric cancer cells

作　　者：徐纪伟[1] 孙丹华[1] 陈旭东[1] XU Ji-wei;SUN Dan-hua;CHEN Xu-dong(Department of Basic Medicine,Luohe Medical College,Luohe 462002,China)

机构地区：[1]漯河医学高等专科学校基础医学部,漯河462002

出　　处：《现代免疫学》2023年第2期95-104,共10页Current Immunology

基　　金：河南省高等学校青年骨干教师培养计划(2017GGJS285);河南省科技厅基础与前沿技术项目(132300410170);河南漯河医学高等专科学校创新创业发展能力提升工程项目(2019LYZKYZD008);漯河医学高等专科学校2022年度科技创新项目(2022KJZD19)。

摘　　要：多能性相关基因2(developmental pluripotency-associated gene 2,DPPA2)在多能性细胞和某些癌组织中特异表达,并有望成为一些恶性肿瘤的特异性免疫治疗靶点。课题组拟研究DPPA2沉默对胃癌细胞SGC-7901生物学行为的影响,为胃癌的治疗提供实验依据。构建DPPA2沉默pGenesil-2/DPPA2重组载体并导入SGC-7901细胞,MTT实验、划痕实验、FACS等研究DPPA2沉默对肿瘤细胞生物学行为的影响,并建立小鼠肾被膜下移植侵袭模型研究肿瘤细胞的在体侵袭能力。结果显示,沉默DPPA2后,DPPA2、NANOG同源盒(NANOG homeobox,NANOG)和八聚体结合转录因子4(octamer binding transcription factor 4,OCT4)mRNA及蛋白表达量在SGC-7901细胞中显著降低(均P<0.01);SGC-7901细胞的增殖、迁移能力减弱,DPPA2沉默后肿瘤细胞停滞于G0/G1期,且能够促进SGC-7901细胞的凋亡;小鼠肾被膜下移植侵袭模型表明,DPPA2沉默可抑制肿瘤细胞对正常组织的局部浸润,减少肿瘤细胞对肾皮质的侵袭。结果显示,DPPA2沉默后胃癌细胞SGC-7901的生物学行为明显被抑制,表明DPPA2在促进胃癌发生、发展过程中发挥着重要的作用,沉默DPPA2可抑制NANOG、OCT4的表达,抑制肿瘤细胞对正常组织的局部浸润,达到影响胃癌细胞生物学行为的目的。Developmental pluripotency-associated gene 2(DPPA2) is specifically expressed in pluripotent cells and certain cancer tissues, and is expected to become a new target for immunotherapy of some cancers. This study intended to elucidate the effect of DPPA2 gene silencing on the biological behavior of gastric cancer cell SGC-7901 and to provide experimental evidence for the potential treatment of gastric cancer. For this purpose, DPPA2 gene-silencing pGenesil-2/DPPA2 recombinant vector was constructed and introduced into SGC-7901 cells. MTT assay, scratch assay, and FACS analysis were used to study the biological behavior of the cells after DPPA2 gene silencing. In addition, a mouse subcapsular transplantation invasive model was established to study the invasion of cancer cells in vivo. The results showed that after DPPA2 gene silencing, the mRNA and protein expressions of DPPA2, NANOG homeobox(NANOG), and octamer binding transcription factor 4(OCT4) were all significantly decreased(all P<0.01). The proliferation and migration abilities of SGC-7901 cells were also weakened. DPPA2 silencing caused cancer cell arresting at G0/G1 phase and promoted the apoptosis of SGC-7901 cells. In addition, the subcapsular transplantation invasive model showed that DPPA2 silencing inhibited the local infiltration of cancer cells into normal tissues and relieved the invasion of cancer cells into the renal cortex. Altogether, our results suggest that DPPA2 plays an important role in promoting the occurrence and development of gastric cancer and that DPPA2 silencing significantly changes the biological behavior of gastric cancer cells by down-regulating the expression of NANOG, OCT4 and by restricting the local infiltration of cancer cells into normal tissues.

关 键 词：胃癌 多能性相关基因2 基因沉默 生物学行为 质粒载体 

分 类 号：R392.12[医药卫生—免疫学]